New research points to inflammation within the brain as a critical contributor
to neuronal abnormalities leading to Alzheimer's disease (AD) and suggests
that early and prolonged treatment with common nonsteroidal anti-inflammatory
drugs (NSAIDs) could block this inflammation before the disease establishes
itself.
AD is the most common dementing disorder of late life, one of many neurodegenerative conditions characterized by chronic neuroinflammation. Microglia are immune cells of the brain and have been found to be highly active and in close proximity to senile plaques, the primary pathological brain abnormality observed at autopsy in the AD brain.
Microglia migrate rapidly to senile plaques and are capable of removing small filaments (amyloid-beta fibrils) of the plaque. However, whether inflammatory changes within the microglia also contribute to the early stages of AD progression has been unclear.
Bruce T. Lamb, PhD, Neurosciences, helped lead a research project showing that microglia-mediated inflammation is, indeed, an early manifestation of AD and often occurs long before symptoms of the disease become apparent.
The researchers found that early neuroinflammation can be blocked with chronic administration of two commonly used NSAIDs - ibuprofen and naproxen. Such early blocking of neuroinflammation significantly improves the likelihood that AD progression can be slowed or prevented altogether.
However, additional studies have demonstrated that once these neuronal alterations have occurred, NSAIDs cannot reverse the effects of inflammation.
"This study argues that both amyloid-beta and neuroinflammation are involved in the abnormal neuronal activity that's part of early AD progression. It also provides a potential explanation of previous successes and failures of NSAIDs as a treatment option for AD patients," Dr. Lamb said. "We suggest that early identification of neuroinflammation might be a viable biomarker to assess a person's risk of AD. This earlier assessment could allow a high-risk person to start beneficial NSAID treatment at a time when it's most likely to slow or stop the disease's progression."
Dr. Lamb's colleagues included Nicholas H. Varvel and Kiran Bhaskar, PhD, of the Institute's Department of Neurosciences; Maria Z. Kounnas, PhD, and Steven L. Wagner, PhD, of Torrey Pines Therapeutics, Inc., La Jolla, CA; Yan Yang, MD, PhD, of Case Western Reserve University's School of Medicine; and Karl Herrup, PhD, Rutgers University's Department of Cell Biology and Neuroscience, Piscataway, NJ. The research appeared in Journal of Clinical Investigation (www.jci.org/, 2009 Nov 9. pii 39716. doi: 10.1172/JCI39716).